Peripheral administration of human recombinant ApoJ/clusterin modulates brain beta-amyloid levels in APP23 mice

@article{deRetana2019PeripheralAO,
  title={Peripheral administration of human recombinant ApoJ/clusterin modulates brain beta-amyloid levels in APP23 mice},
  author={Sof{\'i}a Fern{\'a}ndez de Retana and Paula Marazuela and Montse Sol{\'e} and Guillem Colell and Anna Bonaterra and Jos{\'e} Luis S{\'a}nchez-Quesada and Joan Montaner and Daniel Maspoch and Mary Cano-Sarabia and Mar Hern{\'a}ndez-Guillamon},
  journal={Alzheimer's Research \& Therapy},
  year={2019},
  volume={11}
}
BackgroundApoJ/clusterin is a multifunctional protein highly expressed in the brain. The implication of ApoJ in β-amyloid (Aβ) fibrillization and clearance in the context of Alzheimer’s disease has been widely studied, although the source and concentration of ApoJ that promotes or inhibits Aβ cerebral accumulation is not clear yet. ApoJ is abundant in plasma and approximately 20% can appear bound to HDL-particles. In this regard, the impact of plasmatic ApoJ and its lipidation status on… 

Figures and Tables from this paper

Astrocyte-derived clusterin suppresses amyloid formation in vivo
TLDR
It is demonstrated that CLU plays a major role in Aβ accumulation in the brain and suggest that efforts aimed at CLU upregulation via pharmacological or gene delivery approaches offer a promising therapeutic strategy to regulate amyloid pathology.
Clusterin in Alzheimer’s Disease: An Amyloidogenic Inhibitor of Amyloid Formation
TLDR
These findings elucidate parts of the molecular mechanism in which clusterin inhibits amyloid formation and hint that molecular chaperones withAmyloidogenic properties might have a role in the regulation of amyloidal formation, essentially acting as functional amyloids.
Clusterin in Alzheimer’s disease: an amyloidogenic inhibitor of amyloid formation
TLDR
These findings elucidate parts of the molecular mechanism in which clusterin inhibits amyloid formation and hint that molecular chaperones withAmyloidogenic properties might have a role in the regulation of amyloidal formation, essentially acting as functional amyloids.
Clusterin in Alzheimer's disease: An amyloidogenic inhibitor of amyloid formation?
HDL Proteome and Alzheimer’s Disease: Evidence of a Link
TLDR
The present review summarizes and critically examine the current state of knowledge on the role of these atheroprotective HDL-associated proteins in AD pathogenesis and physiopathology.
HDL Accessory Proteins in Parkinson’s Disease—Focusing on Clusterin (Apolipoprotein J) in Regard to Its Involvement in Pathology and Diagnostics—A Review
TLDR
In this review, the association of clusterin with PD is delineated, with respect to its putative involvement in the pathological mechanism and its application in PD prognosis/diagnosis.
The Role of HDL and HDL Mimetic Peptides as Potential Therapeutics for Alzheimer’s Disease
TLDR
The current evidence for the role of HDL in AD and the potential of using small peptides mimicking HDL or its associated apolipoproteins (HDL-mimetic peptides) as therapeutics to treat AD are described.
Decreased levels of circulating trimethylamine N-oxide alleviate cognitive and pathological deterioration in transgenic mice: a potential therapeutic approach for Alzheimer’s disease
TLDR
It is demonstrated that elevated circulating TMAO during the aging process might deteriorate cognitive function and pathology in APP/PS1 mice.
Albumin domain mutants with enhanced Aβ binding capacity identified by phage display analysis for application in various peripheral Aβ elimination approaches of Alzheimer's disease treatment
TLDR
The Aβ binding site on HSA is identified and HSA mutants with high binding capacities for Aβ are developed using a phage display method and these mutants exhibited stronger scavenging abilities than the wild type, as revealed via in vitro equilibrium dialysis of Aβ experiments.
Endogenous Human Proteins Interfering with Amyloid Formation
TLDR
The properties of transthyretin, apolipoprotein E, clusterin, and BRICHOS protein domain which all effectively interfere with amyloid in vitro, as well as displaying a clinical impact in humans or animal models are reviewed.
...
1
2
...

References

SHOWING 1-10 OF 74 REFERENCES
Modulation of Amyloid-β1-40 Transport by ApoA1 and ApoJ Across an in vitro Model of the Blood-Brain Barrier.
TLDR
The present study highlights the role of ApoJ and ApoA1 in the in vitro modulation of Aβ elimination across the BBB and its modulation by the natural chaperones Apolipoprotein A1 (ApoA1) and Apoliprotein J/Clusterin (A poJ).
Characterization of ApoJ-reconstituted high-density lipoprotein (rHDL) nanodisc for the potential treatment of cerebral β-amyloidosis
TLDR
It was confirmed that rHDL-rApoJ accumulated in the cranial region, especially in old transgenic mice presenting a high cerebral Aβ load, which may be potentially considered as a therapeutic option for β-amyloid-related pathologies.
Clearance of amyloid-β peptide across the blood-brain barrier: Implication for therapies in Alzheimer’s disease
TLDR
Therapies to increase LRP1 expression or reduce RAGE activity at the BBB and/or restore the peripheral Aβ ‘sink’ action, hold potential to reduce brain Aβ and inflammation, and improve CBF and functional recovery in AD models, and by extension in AD patients.
Human Apolipoprotein E4 Alters the Amyloid-β 40:42 Ratio and Promotes the Formation of Cerebral Amyloid Angiopathy in an Amyloid Precursor Protein Transgenic Model
TLDR
It is demonstrated that, once Aβ fibrillogenesis occurs, apoE4 favors the formation of CAA over parenchymal plaques and suggest that molecules or treatments that increase the ratio of Aβ 40:42 may favor the formationof CAA versus paren chymic plaques.
Clusterin levels are increased in Alzheimer's disease and influence the regional distribution of Aβ
TLDR
It is indicated that in AD, clusterin increases, particularly in regions with most abundant Aβ, but because the increase does not match the rising level of Aβ42, the molar ratio of clusterin : A β42 in those regions falls, probably contributing to Aβ deposition within the tissue.
Brain uptake of circulating apolipoproteins J and E complexed to Alzheimer's amyloid beta.
TLDR
It is concluded that sA beta 1-40 binding to apo J and apo E results in significant (> 100-fold) difference in brain uptake of their respective complexes, and it is hypothesize that in normal brain apoJ facilitates sAbeta transport.
Clearance of amyloid-beta peptide across the blood-brain barrier: implication for therapies in Alzheimer's disease.
TLDR
Therapies to increase LRP1 expression or reduce RAGE activity at the BBB and/or restore the peripheral Abeta 'sink' action, hold potential to reduce brain Abeta and inflammation, and improve CBF and functional recovery in AD models, and by extension in AD patients.
Role of clusterin in the brain vascular clearance of amyloid-β
TLDR
Failed transvascular clearance of brain Aβ across the blood–brain barrier plays an important role in Aβ accumulation in the brain, both in human AD and animal models and in PNAS, the effect of endogenous murine Clu deficiency on Aβ pathology is explored.
...
1
2
3
4
5
...